Evaluation of cytotoxic activities of snake venoms toward breast (MCF-7) and skin cancer (A-375) cell lines
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Snake venoms are mixtures of bioactive proteins and peptides that exhibit diverse biochemical activities. This wide array of pharmacologies associated with snake venoms has made them attractive sources for research into potentially novel therapeutics, and several venom-derived drugs are now in use. In the current study we performed a broad screen of a variety of venoms (61 taxa) from the major venomous snake families (Viperidae, Elapidae and “Colubridae”) in order to examine cytotoxic effects toward MCF-7 breast cancer cells and A-375 melanoma cells. MTT cell viability assays of cancer cells incubated with crude venoms revealed that most venoms showed significant cytotoxicity. We further investigated venom from the Red-bellied Blacksnake (Pseudechis porphyriacus); venom was fractionated by ion exchange fast protein liquid chromatography and several cytotoxic components were isolated. SDS-PAGE and MALDI-TOF mass spectrometry were used to identify the compounds in this venom responsible for the cytotoxic effects. In general, viper venoms were potently cytotoxic, with MCF-7 cells showing greater sensitivity, while elapid and colubrid venoms were much less toxic; notable exceptions included the elapid genera Micrurus, Naja and Pseudechis, which were quite cytotoxic to both cell lines. However, venoms with the most potent cytotoxicity were often not those with low mouse LD50s, including some dangerously venomous viperids and Australian elapids. This study confirmed that many venoms contain cytotoxic compounds, including catalytic PLA2s, and several venoms also showed significant differential toxicity toward the two cancer cell lines. Our results indicate that several previously uncharacterized venoms could contain promising lead compounds for drug development.
KeywordsColubridae Cytotoxicity Drug development Melanoma Phospholipase A2 Three-finger toxin
Funding for this project was provided by a grant (to SPM) from the Colorado Office of Economic Development and Trade (COEDIT), Bioscience Discovery Evaluation Grant Program. Additional funding was provided by the UNC Office of Sponsored Programs. We thank Peter J. Mirtschin of Venom Supplies Pty. Ltd. for providing P. porphyriacus venom, Dr. Charlotte Ownby of Oklahoma State University for numerous elapid and viperid venoms, and A. Ah-Young, B. Heyborne, J. LeRoy Waite, and A. Wastell for assistance with venom extractions (rattlesnakes and colubrids).
Conflict of interest
The authors state that there are no conflicts of interest.
All vertebrate animal manipulations (venom extractions of snakes) were in accordance with protocols approved by the UNC IACUC.
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